Digital gene expression profiling analysis of A549 cells cultured with PM10 in moxa smoke

Background:Moxibustion is a traditional Chinese medicine therapy to cure diseases by fumigating meridians or affected parts via burning of moxa floss.Moxa smoke(MS)is one of the key factors in moxibustion.In this study,we adopted digital gene expression profiling,a next-generation gene sequencing technology,to investigate the effect of MS,inhalable particulate matter(PM10),on human lung adenocarcinoma A549 cells.Methods:The effects of MS PM10 on A549 cells,over different treatment durations were investigated in different groups:the 4-h group(4-h MS group and 4-h control group)and the 20-h group(20-h MS group and 20-h control group).Samples collected from the four groups were stored at
80C for subsequent digital gene expression analysis.The differentially expressed genes(DEGs),identified after PM10 treatment,were screened,and their expression patterns analyzed by cluster analysis,Gene Ontology term enrichment,and Kyoto Encyclopedia of Genes and Genomes pathway analysis.Results:Compared with two control groups,1109 DEGs were identified after 4 h of MS intervention and 3565 DEGs were found after 20 h of MS intervention,respectively.Compared with that after 4-h intervention,2149 DEGs were identified after 20-h intervention.Cluster analysis demonstrated that PM10 can significantly inhibit cell cycle process with the prolongation of intervention time.Significant pathway enrichment analysis showed that MS PM10 can inhibit A549 cell cycle process at all phases.When MS PM10 exposure time prolongs,the inhibitory effect on cell cycle process becomes more obvious.Conclusion:MS PM10 has many biological activities,and may cause differential expression of genes involved in various biological processes.Nevertheless,further research on MS is warranted for better understanding of the mechanistic details.

Research on the Influence of Interest Rate Liberalization on Commercial Banks' Profitability in China

In order to explore the influence of interest rate liberalization on profitability,an empirical analysis is carried out with the panel data of commercial banks in China from 2009 to 2019.Then,the heterogeneity of the impact is studied among different banks.The results show that,first,interest rate liberalization and commercial banks'profitability have an inverted U-shaped relationship,whereby interest rate liberalization would increase the profitability of banks in the early stage but would reduce the profitability after reaching a peak inflection point at the later stage.Secondly,the impact varies among different banks,being more significant in urban commercial banks and large state-owned banks.

Allele-defined genome reveals biallelic differentiation during cassava evolution

Dear Editor,Generation of heterozygous genomes by hybridization between or within species can help maintain plant diversity and serve as a potential source of new species(Baek et al.,2018).Moreover,genomic heterozygosity is associated with genomic coadaptation,developmental stability,and heterosis.Accurate definition of alleles in haplotypes is necessary to precisely characterize allelic variation controlling agriculturally important traits(Shi et al.,2019).Currently,most released genomes have mosaic assembly of haplotypes due to random selection or collapse of alleles during genome assembly(Shi et al.,2019),which masked allelic variation and functional differentiation of divergent alleles in heterozygous species.

Repurposing of antitumor drug candidate Quisinostat lead to novel spirocyclic antimalarial agents

Antimalarial chemotherapies endowed with effectiveness against drug-resistant parasites and good safety are urgently required in clinical.Our previous research revealed that clinical phaseⅡantitumor drug Quisinostat was a promising antimalarial prototype by inhibiting the activity of Plasmodium falciparum(P.falciparum)histone deacetylase(PfHDAC).Herein,30 novel spirocyclic linker derivatives were designed and synthesized based on Quisinostat as lead compound,and then their antimalarial activities and cytotoxicity were systematically evaluated.Among them,compounds 8 and 27 could effectively eliminate wild-type and multi-drug resistant P.falciparum parasites,and display weakened cytotoxicity and good metabolic stability.Western blot assay demonstrated that they could inhibit PfHDAC activity like Quisinostat.In addition,both 8 and 27 showed certain antimalarial efficacy in rodent malaria model,and the animal toxicity of 8 was significantly improved compared with Quisinostat.Overall,8 and 27 were structurally novel PfHDAC inhibitors and provided prospective prototype for further antimalarial drug research.

Transcriptional landscape of rice roots at the single-cell resolution

There are two main types of root systems in flowering plants,namely taproot systems of dicots and fibrous root systems found in monocots.Despite this fundamental split,our current knowledge of cellular and molecular mechanism driving root development is mainly based on studies of the dicot model Arabidopsis.However,the world major crops are monocots and little is known about the transcriptional programs underlying cell-type specification in this clade.Here,we report the transcriptomes of more than 20000 single cells derived from root tips of two agronomically important rice cultivars.Using combined computational and experimental analyses we were able to robustly identify most of the major cell types and define novel cell-type-specific marker genes for both cultivars.Importantly,we found divergent cell types associated with specific regulatory programs,including phytohormone biosynthesis,signaling,and response,which were well conserved between the two rice cultivars.In addition,we detected substantial differences between the cell-type transcript profiles of Arabidopsis and rice.These species-specific features emphasize the importance of analyzing tissues across diverse model species,including rice.Taken together,our study provides insight into the transcriptomic landscape of major cell types of rice root tip at single-cell resolution and opens new avenues to study cell-type specification,function,and evolution in plants.

Cucurbitacin B-induced G2/M cell cycle arrest of conjunctival melanoma cells mediated by GRP78-FOXM1-KIF20A pathway

Conjunctival melanoma(CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B(CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16,CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a Kdvalue of0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.

Synthesis of (±)-Bakuchiol via a Pot-Economy Approach

A rapid synthetic route toward(±)-Bakuchiol is presented in 29%overall yield.After the sole all-carbon quaternary carbon center is created via allylboration of 2-aryl acetaldehyde,a“Pot-Economy”approach including mesylation,elimination,and desilylation was realized in the presence of ^(t)BuOK under ambient temperature to provide(±)-Bakuchiol.